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Defects in monoamine neurotransmitter systems are implicated in DS and AD but have not been comprehensively studied in DS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Noradrenaline, adrenaline, and their metabolite 3\u2010methoxy\u20104\u2010hydroxyphenylglycol (MHPG); dopamine and its metabolites 3,4\u2010dihydroxyphenylacetic acid (DOPAC) and homovanillic acid; and serotonin and its metabolite 5\u2010hydroxyindoleacetic acid were quantified in 15 brain regions of DS without AD (DS, n\u00a0=\u00a04), DS with AD (DS+AD, n\u00a0=\u00a017), early\u2010onset AD (EOAD, n\u00a0=\u00a011) patients, and healthy non\u2010DS controls (n\u00a0=\u00a010) in the general population. Moreover, monoaminergic concentrations were determined in cerebrospinal fluid (CSF)\/plasma samples of DS (n\u00a0=\u00a037\/149), DS with prodromal AD (DS+pAD, n\u00a0=\u00a013\/36), and DS+AD (n\u00a0=\u00a018\/40).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In brain, noradrenergic and serotonergic compounds were overall reduced in DS+AD versus EOAD, while the dopaminergic system showed a bidirectional change. For DS versus non\u2010DS controls, significantly decreased MHPG levels were noted in various brain regions, though to a lesser extent than for DS+AD versus EOAD. Apart from DOPAC, CSF\/plasma concentrations were not altered between groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Monoamine neurotransmitters and metabolites were evidently impacted in DS, DS+AD, and EOAD. DS and DS+AD presented a remarkably similar monoaminergic profile, possibly related to early deposition of amyloid pathology in DS. To confirm whether monoaminergic alterations are indeed due to early amyloid \u03b2 accumulation, future avenues include positron emission tomography studies of monoaminergic neurotransmission in relation to amyloid deposition, as well as relating monoaminergic concentrations to CSF\/plasma levels of amyloid \u03b2 and tau within individuals.<\/jats:p><\/jats:sec>","DOI":"10.1016\/j.dadm.2017.11.001","type":"journal-article","created":{"date-parts":[[2017,11,24]],"date-time":"2017-11-24T07:15:56Z","timestamp":1511507756000},"page":"99-111","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Monoaminergic impairment in Down syndrome with Alzheimer's disease compared to early\u2010onset Alzheimer's disease"],"prefix":"10.1002","volume":"10","author":[{"given":"Alain D.","family":"Dekker","sequence":"first","affiliation":[{"name":"Department of Neurology and Alzheimer Research Center University of Groningen, University 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